Diffuse Idiopathic Skeletal Hyperostosis
Diffuse idiopathic skeletal hyperostosis (DISH) is a noninflammatory condition causing calcification and ossification of spinal ligaments and entheses. It is also known as ankylosing hyperostosis, Forestier disease, and Forestier-Rotes-Querol disease. The condition may be asymptomatic, or may be associated with spinal pain.
Aetiology
The cause of DISH is unknown, however it has been thought that certain factors may be important in its development. These include mechanical factors, diet, drugs, environmental exposures, and metabolic conditions. It is thought that there is abnormal osteoblastic differentiation and activity located at the entheses, as some patients may be deficient in certain inhibitors of bone formation such as Dickkopf-1 and matrix Gla protein.
- Mechanical factors
A right-sided prominence of bony bridging is seen at the thoracic spine. There may be mechanical factors associated with the location of the aorta. Interestingly, in those with dextrocardia or situs inversus, the bony bridging is more prominent on the left.
Mechanical forces may affect bone formation. In those with ossification of hte posterior longitudinal ligament (may occur with DISH or independently), ligamentous stretching can increase prostaglandin I2 synthase which results in stimulation of osteogenic differentation. Dickkopf-1, an inhibitor of osteoblastogenesis, may be reduced in those with DISH thereby promoting hyperostosis.
There does not appear to be a difference in the amount of heavy work done in those with DISH compared to controls.
- Environmental factors and diet
Fluoride has been investigated but found unlikely to be a cause. There are mixed reports of the association between higher serum retinol (signifying excessive vitamin A exposure) levels and DISH.
- Medications
Isotretinoin, which is a derivative of vitamin A, and other retinoids are associated with hyperostosis, but more-so in extraspinal areas.
- Metabolic conditions
It is thought that metabolic factors many contribute to increased osteoblastic activity in DISH. Some studies report increased levels of insulin, insulin-like growth factor 1, and growth hormone. Insulin-like growth factor 1 stimulates osteoblasts, and growth hormone can increase the production of this factor.
There are some intriguing demographic studies looking at the association between DISH and metabolic conditions. The Pima Native American people have both a high incidence of DISH and metabolic conditions such as obesity, hypertension, diabetes mellitus, and hyperinsuliaemia. DISH appears to be more common in obese Caucasian people, and possibly also in those with diabetes mellitus. DISH is also seen in up to 20 percent in acromegalic patients.
Also seen in the condition is increased vascularity of the ossified ligaments. It is not known whether this is a cause or a downstream effect of DISH.
Other factors have been studied in their role in DISH. Platelet-derived growth factor-BB and transforming growth factor-1-beta in the cells of ligaments can increase levels of nuclear factor kappa B. Nuclear factor kappa B can promote osteoblastogenesis. Curiously, there are elevated levels of matrix Gla in DISH, but this protein is thought to inhibit bone formation.
